ArticleJournal of experimental & clinical cancer research : CR2019
Ischemia reperfusion injury promotes recurrence of hepatocellular carcinoma in fatty liver via ALOX12-12HETE-GPR31 signaling axis.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- The role of machine perfusion in preventing recurrence after liver transplant for hepatocellular carcinoma: a systematic review and meta-analysis.BMC gastroenterology · 2026Pooled it
- Apiotrichum-Centered Fungal Interaction Network Disturbance Correlates With Increased Arterial Stiffness.Aging cell · 2026Article
- Lidocaine inhibits hepatocellular carcinoma cell proliferation, migration, and invasion through the downregulation of SLC6A3.Scientific reports · 2026Article
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- MAGL Inhibition Relieves Psoriasiform Inflammation and Pruritus Via Modulation of ALOX12-12-HETE Axis in Mice.Inflammation · 2026Article
- N-acetylcysteine modulates neutrophil-driven immune and metabolic pathways in steatotic liver ischemia-reperfusion injury.Frontiers in immunology · 2026Article
- Ursolic acid mitigates hepatic ischemia-reperfusion injury by regulating the ALOX12/12(S)-HETE and PTGES/prostaglandin E2 axis via arachidonic acid metabolism pathway.Frontiers in pharmacology · 2026Article
- Thrombomodulin Mitigates the Progression of Hepatocellular Carcinoma in Steatotic Liver.Journal of hepatocellular carcinoma · 2026Article
- Liver ischemia-reperfusion promotes tumor metastasis via neutrophil-endothelial interactions: targeting ICAM1 to prevent metastatic recurrence.Journal of translational medicine · 2025Article
- Integrated screening identifies GPR31 as a key driver and druggable target for metabolic dysfunction-associated steatohepatitis.The Journal of clinical investigation · 2025Article
- Arachidonic acid metabolism in metabolic dysfunction-associated steatotic liver disease and liver fibrosis.Hepatology communications · 2025Review
- Liver Transplantation for Cancer-Current Challenges and Emerging Solutions.Journal of clinical medicine · 2025Review
- Resolution of experimental malaria-associated acute respiratory distress syndrome is Alox12 independent and shows residual inflammation.Malaria journal · 2025Article
- Huangqin decoction inhibits colorectal inflammatory cancer transformation by improving gut microbiome-mediated metabolic dysfunction.Journal of pharmaceutical analysis · 2025Article
- Genome-wide KAS-Seq mapping of leukocytes in ischemia-reperfusion model reveals IL7R as a potential therapeutic target for ischemia-reperfusion injury.Scientific reports · 2025Article
- Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers.Molecular and cellular biochemistry · 2025Review
- Article
- CKS2 Mediates Hepatocellular Carcinoma Recurrence After Hepatic Ischemia-Reperfusion Injury Related to M2 Macrophages.Journal of inflammation research · 2025Article
- Comprehensive characterization and metabolomics to explore the role of hydrocortisone-induced yin deficiency syndrome in mice.Biochemistry and biophysics reports · 2024Article
- The pyruvate-GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIschemia reperfusion injury (IRI) has been shown to increase the risk of tumor recurrence after liver surgery. Also, nonalcoholic fatty liver disease (NAFLD) is associated with increased HCC recurrence. ALOX12-12-HETE pathway is activated both in liver IRI and NASH. Also, ALOX12-12-HETE has been shown to mediate tumorigenesis and progression. Therefore, our study aims to investigate whether the ALOX12-12-HETE-GPR31 pathway involved in IRI induced HCC recurrence in NAFLD.
methodsHCC mouse model was used to mimic the HCC recurrence in NAFLD. Western Blot, qPCR, Elisa and Immunofluorescence analysis were conducted to evaluate the changes of multiple signaling pathways during HCC recurrence, including ALOX12-12-HETE axis, EMT, MMPs and PI3K/AKT/NF-κB signaling pathway. We also measured the expression and functional changes of GPR31 by siRNA.
resultsALOX12-12-HETE pathway was activated in liver IRI and its activation was further enhanced in NAFLD, which induced more severe HCC recurrence in fatty livers than normal livers. Inhibition of ALOX12-12-HETE by ML355 reduced the HCC recurrence in fatty livers. In vitro studies showed that 12-HETE increased the expression of GPR31 and induced epithelial-mesenchymal transition (EMT) and matrix metalloprotein (MMPs) by activating PI3K/AKT/NF-κB pathway. Furthermore, knockdown of GPR31 in cancer cells inhibited the HCC recurrence in NAFLD.
conclusionsALOX12-12-HETE-GPR31 played an important role in HCC recurrence and might be a potential therapeutic target to reduce HCC recurrence after surgery in fatty livers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.